{"doi":"10.1016/j.str.2009.06.008","title":"The Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways","abstract":null,"journal":"Structure","year":2009,"id":676802,"datarank":0.8914199062690054,"base_score":5.942799375126701,"endowment":5.942799375126701,"self_citation_contribution":0.8914199062690054,"citation_network_contribution":0.0,"self_endowment_contribution":0.8914199062690054,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":380,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1768343,"name":"Chung-Jung Tsai","orcid":null,"position":1,"is_corresponding":false},{"id":385079,"name":"Buyong Ma","orcid":"0000-0002-7383-719X","position":2,"is_corresponding":false},{"id":70301,"name":"Ruth Nussinov","orcid":"0000-0002-8115-6415","position":3,"is_corresponding":false},{"id":345875,"name":"Antonio del Sol","orcid":"0000-0002-9926-617X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways","abstract":"Although allostery draws increasing attention, not much is known about allosteric mechanisms. Here we argue that in all proteins, allosteric signals transmit through multiple, pre-existing pathways; which pathways dominate depend on protein topologies, specific binding events, covalent modifications, and cellular (environmental) conditions. Further, perturbation events at any site on the protein surface (or in the interior) will not create new pathways but only shift the pre-existing ensemble of pathways. Drugs binding at different sites or mutational events in disease shift the ensemble toward the same conformations; however, the relative populations of the different states will change. Consequently the observed functional, conformational, and dynamic effects will be different. This is the origin of allosteric functional modulation in dynamic proteins: allostery does not necessarily need to invoke conformational rearrangements to control protein activity and pre-existing pathways are always defaulted to during allostery regardless of the stimulant and perturbation site in the protein.","is_dataset_classified":null,"base_score":5.942799375126701,"endowment":5.942799375126701,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19679084","pmcid":"PMC2749652","openalex_id":"https://openalex.org/W2083975423","authors":[],"funders":[{"funder_name":"CCR NIH HHS","grant_id":"HHSN261200800001C","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"Z01 BC010441","title":null},{"funder_name":"NCI NIH HHS","grant_id":"HHSN261200800001E","title":null}],"total_grants":3,"fwci":12.222,"citation_percentile":0.99209739,"influential_citations":0,"citation_trend":[{"year":2012,"count":29},{"year":2013,"count":38},{"year":2014,"count":38},{"year":2015,"count":21},{"year":2016,"count":32},{"year":2017,"count":14},{"year":2018,"count":15},{"year":2019,"count":22},{"year":2020,"count":22},{"year":2021,"count":18},{"year":2022,"count":15},{"year":2023,"count":13},{"year":2024,"count":11},{"year":2025,"count":16},{"year":2026,"count":7}],"oa_status":"bronze","license":"https://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.cell.com/article/S0969212609002500/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S0969212609002500/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212609002500?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212609002500?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.str.2009.06.008","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19679084","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2749652","host_type":"repository"}],"fields_of_study":["Protein Structure and Dynamics","Enzyme Structure and Function","Computational Drug Discovery Methods"],"mesh_terms":["Allosteric Regulation","Binding Sites","Models, Molecular","Mutation","Protein Binding","Protein Conformation","Proteins","Drug Design","Signal Transduction","Protein Structure, Tertiary"],"keywords":["Allosteric regulation","Allosteric enzyme","Signaling proteins","Binding site","Plasma protein binding","Conformational change","Protein structure","Biophysics","Chemistry","Signal transduction","Computational biology","Biology","Biochemistry","Enzyme"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T03:07:32.291973Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}